Enfortumab Vedotin-ejfv

Eli Lilly has shared first-in-human results for its selective FGFR3 inhibitor in a subset of bladder cancer patients, marking the start of a program that could eventually challenge Johnson & Johnson’s Balversa. Balversa is marketed for metastatic FGFR3-altered bladder cancer in the US, but the drug’s broad spectrum inhibition of FGFR means it comes with a host of serious side effects. The medicine is “extremely difficult to stay on” with patients often tapering doses, Lilly’s head of oncology Jacob Van Naarden told Endpoints News in an interview ahead of the confab. By contrast, Lilly’s LOXO-435 selectively targets the FGFR3 isoform, homing in on the somatic alteration that drives the cancer to avoid off-target effects. Lilly’s Phase 1 data from 70 patients with various solid tumors given a 200 mg or higher dose of the drug showed its most common side effect was diarrhea (76%). The side effect was mostly low-grade and manageable, according to data presented Friday at the ASCO genitourinary cancer symposium in San Francisco. Retinopathy and onycholysis were rare and treatment discontinuation rates for all doses 200 mg or higher were in the single-digit percentages, according to Lilly. Balversa patients experience serious retinal toxicities and hyperphosphatemia as well as fatigue and onycholysis. LOXO-435’s safety profile seems “similar to or slightly worse” than that for Tyra Biosciences’ selective FGFR3 inhibitor TYRA-300, Jefferies analysts said Monday when Lilly’s abstract was published on the confab website. In Tyra’s Phase 1/2 trial, its drug was associated with a lower rate of diarrhea (20%) and hyperphosphatemia (13% versus 28% for LOXO-435) in patients with FGFR3-altered metastatic urothelial carcinoma. But LOXO-435 saw fewer cases of increases in certain liver enzymes (22%) versus TYRA-300 (47%). As for efficacy, LOXO-435 is “on par with what we expect for this class” and “probably in the same ballpark as pan-FGFR inhibitors,” Lilly’s clinical lead for the program Arjun Balar told Endpoints. In Lilly’s study, LOXO-435 achieved a 41% confirmed overall response rate when given at doses of at least 200 mg to 39 patients with metastatic FGFR3-altered bladder cancer, according to Friday’s data. Tyra’s candidate hit a higher ORR of around 55% in its study, the Jefferies analysts highlighted. But “it’s very difficult to make any sort of comparisons [across trials] within Phase 1 patient populations,” Balar said. Tyra’s data came from just 11 subjects with a median of two prior lines of therapy versus three for the patients enrolled in Lilly’s trial. Lilly will now focus on refining an optimal dose of its drug and enrolling various expansion cohorts, including one evaluating a triplet regimen of LOXO-435, Pfizer/Seagen’s Padcev and Merck’s Keytruda in relevant patients with first-line metastatic bladder cancer. Other cohorts will include patients previously treated with Balversa and those naive to Balversa, Balar said. The company’s “ultimate goal” is to capture the market of around 15,000 patients worldwide with FGFR3-altered metastatic urothelial carcinoma, he added.

Safety is one area Corbus could differentiate its ADC.\n Corbus Pharmaceuticals has posted the first Western clinical data on its would-be rival to Pfizer’s Padcev. The overall readout is in line with the Chinese data that drummed up excitement in the antibody-drug conjugate (ADC) last year, but investors sent Corbus’ stock down 10% in premarket trading.Massachusetts-based Corbus licensed the Nectin-4-directed ADC in 2023. The deal saw China’s CSPC Pharmaceutical grant Corbus rights to the drug candidate in markets including the U.S. and European Union in return for $7.5 million upfront. The next year, CSPC reported a 28% response rate in 25 people in a Chinese phase 1 trial, offering early encouragement that the ADC could be a challenger to Padcev.Friday, Corbus shared new data at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium that suggest the efficacy seen in the Chinese trial has translated to Western populations. The new data come from a phase 1 trial that enrolled patients in the U.S. and U.K.Corbus reported a 27% response rate in 26 evaluable patients in the Western trial. The study mirrored the four highest doses used in the Chinese trial but featured some differences. Corbus included a wider range of tumor types and, unlike CSPC, allowed patients to enroll regardless of their individual Nectin-4 levels. The biotech reported responses in patients with low H-scores for Nectin-4. Like in the Chinese trial, Corbus saw responses in patients with bladder and cervical cancer. The bladder data may be what has investors antsy, with the biotech reporting one response in four patients. The 25% response rate is down from the 44% seen in nine patients in China, although the small size of the arm makes it hard to draw conclusions. One of the two cervical cancer patients had a complete response.The Western trial suggests there may also be an opportunity for the ADC in head and neck cancer, with four of the seven patients with that tumor type responding to the therapy. While the cohort is small, the response rate is currently way above the 24% Padcev has achieved in the indication.Corbus is investing in the asset in the belief the ADC has an advantage over Pfizer because it has a longer half-life and lower drug antibody ratio. The biotech believes those differences may translate into reduced dosing frequency and higher doses than Pacdev, an ADC that Pfizer picked up in its $43 billion acquisition of Seagen. Corbus is now working to optimize the ADC dose.Safety is one area Corbus could differentiate its ADC, with the biotech noting fewer patients on the drug candidate had peripheral neuropathy and skin toxicity than in Pacdev studies. Eye disorders looked like a safety concern in the Chinese trial, with 79% of people on one dose having a reaction, but Corbus’ steps seem to have mitigated the risk. Eye reaction rates were lower and no patients dropped out over them.